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Home , Buprenorphine, Mitragyna speciosa, Mitragynine

481 5 g), -like effects at 5 to 15 g, 15 g (Chang-Chien et al., 2017). It < > CASE SUMMARY After hospital discharge, she transferred care to our The first patient is a 60-year-old woman with remote Due to growing number of poison control cases associ- The addictive potential of kratom remains debated. practice where maintenanceof is general offered primary as care. part Shenance declined at buprenorphine mainte- thepregabalin, and initial visit. forshe chronic She was was and no reported longer continued that using on kratom. , history ofchronic pain due dependence totreated (in with and prescription osteoarthritis long-termtially of presented remission), knees for after several unintentionaladmission opioid years. overdose to She requiring the ini- purchased intensive at care a unit gas station, afteroxycodone-acetaminophen, in taking and addition to kratom. prescribed tramadol, Patient 1 23 hours (Chang-Chien et al., 2017). ated with kratom (AnwarFDA et issued al., a 2016), warning in oncomputational February its 2018, model addictive the potential, of2018). citing novel kratom’s opioid properties (FDA, Dependence is commonregularly in Southeast among Asia; however, they personshigh generally levels maintain of who social functioning usea (Singh signal et that kratom patterns al., of 2016). useStates There and is supply may of kratom have in thefrom higher United Internet level shops and of higherkratom doses toxicity in among due persons the who tocases West use adulterants of (Singh patients et who developed al.,were kratom successfully 2016). dependence transitioned and to Here who buprenorphine we maintenance. present 2 weak mu-opioid agonist2016). (Cinosi et A al., second(2% 2015; of key Warner kratom et by component al., weight),is is a 13-times potent 7-hydroxymitragynine more opioid mu-agonistpotent potent which than than mitragyninepounds act and (Cinosi as 46-times weak et antagonists more receptors at the al., in kappa- vitro and 2015). delta-opioid (Kruegelhas Both broad and affinity for Grundmann, com- receptors 2017).ergic, including dopaminergic, serotonergic, Kratom and adren- GABAergic pathways2015). (Cinosi et It al., exhibitsstimulant dose-dependent at low effects, doses ( actingand as sedation at areaches doses mild peak concentration at 0.83 hours with a half-life of EPORT R ASE Mitra- C Megan Buresh, MD Maintenance Two patients using kratom to self-treat chronic Volume 12, Number 6, November/December 2018 tree (Warner et al., 2016). It is largely obtained 2018;12: 481–483) Use of the unregulated herbal supplement kratom is Kratom use is on the rise and with increasing evidence  buprenorphine, , kratom, , 2018 American Society of Medicine ß Kratom contains over 40 structurally related , Copyright © 2018 American Society of . Unauthorized reproduction of this article is prohibited. Copyright © 2018 American Society of Addiction Medicine. Unauthorized reproduction ince the early 2000s,opioid-like use of properties, kratom, an is herbal on with the rise in the West and School of Medicine, Baltimore, MD. dence, Johns HopkinsBuilding, Bayview, West 5200 Tower, 5th Eastern Floor,E-mail: Avenue, Baltimore, [email protected] Mason MD. F. Lord Treatment of Kratom Dependence With Buprenorphine- J Addict Med J Addict Med Received for publication AprilThere 20, are 2018; no accepted outsideThe May sources authors 26, of declare 2018. support noSend requiring conflicts correspondence acknowledgement. of to interest. Megan Buresh, MD, Division of Chemical Depen- Copyright From the Division of Chemical Dependence, Johns Hopkins University Key Words: ( S oxone maintenance via homeopioid withdrawal initiation and with chronic controlConclusions: pain. of both their of developing opioid-type dependenceThis case due series shows to that buprenorphine chronic candependence be kratom used and to use. treat underlying kratom chronic pain that drives it use. who developed kratom dependencecessfully and transitioned withdrawal to who buprenorphine-naloxone wereCase maintenance. suc- Summary: pain after prescription opioidsclinic were discontinued with presenting evidence toexamination, our of both patients kratom showed signs dependenceBoth of mild patients and opioid were withdrawal. withdrawal. successfully On transitioned to buprenorphine-nal- Introduction: on the rise in the United States. We present a case series of 2 patients marketed astherapy a without need cheaper for(Cinosi prescription alternative et or to medical al., supervision 2015; opioid Warner et replacement al.,the 2016). most common of which is mitragynine, which acts as a receiving increasing media andtion (FDA) Food attention, including and Drug ofproducts 100 Administra- cases of in kratom Southeast 2016 Asia, kratom (Voelker, is 2016).gyna obtained speciosa from Used the forfrom of internet centuries and ‘‘legal high’’ in shopstablet, as and raw leaves, concentrated capsules, extracts (Warner et al., 2016). It is ISSN: 1932-0620/18/1206-0481 DOI: 10.1097/ADM.0000000000000428

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After several months of follow-up, she admitted that she Galbis-Reig, 2016). Kratom dependence and withdrawal is had been unable to stop using kratom due to rebound pain and common in persons who use kratom regularly in Southeast withdrawal symptoms when she attempted to decrease her Asia (Singh et al., 2014). Most clinical information that we dose. The decision was made to discontinue tramadol and have about the clinical effects of kratom in the West are transition to buprenorphine via home initiation. At time of limited to self-report data and poison control series. initiation, she was using 0.25 ounces kratom every 4 hours, Persons who use kratom report beneficial effects of purchased over Internet from supplier in the Philippines, as relaxation, pain relief, increased energy, and decrease in well as prescribed tramadol. On examination, she presented (Swogger et al., 2015; Grundmann, 2017). Com- with mild (rhinorrhea, irritability). Urine mon side effects reported by users include stomach upset, toxicology was positive for tramadol and negative for , , itching and mild sedation (Swogger et al., 2015) and , methadone, buprenorphine and other illicit . , agitation/irritability, drowsiness, nausea, and She was transitioned to sublingual buprenorphine-nal- hypertension in Poison Control calls (Anwar et al., 2016). oxone from kratom using home induction. She waited Among case series of 12 patients from poison control 17 hours from last kratom and tramadol use and subjective centers, the main clinical effects were (25%), altered withdrawal (rhinorrhea, irritability, and increased pain) before mental status, agitation, central nervous system depression taking first dose of buprenorphine-naloxone (bup-nx). She and tachycardia (Cumpston et al., 2018). Reported fatalities took 4-1 mg bup-nx on first evening, then increased dose to 4- after kratom use have been in the setting of polysubstance use 1 mg SL bup-nx 4 times daily. She reported resolution of her (Neerman et al., 2013; McIntyre et al., 2015). Kratom is not pain symptoms after transition to buprenorphine and follow- detected by conventional drug screening tests; it requires up urine drug testing has been negative for full- opioids advanced test like liquid chromatography-tandem or ion-mass and positive for buprenorphine/. In 9 months spectrometry (Cinosi et al., 2015). of follow-up, she continues to have excellent pain control and In an online survey of people who use kratom in the is achieving her functional goals. She has also decreased her United States, participants were predominantly male, age 21 dose from 300 mg PO bid to 200 mg PO bid. to 50, white, employed, and had some college education (Grundmann, 2017). Similar to the cases presented here, many Patient 2 reported use of kratom for self-treatment of pain (Grundmann, The second patient is a 57-year-old man with chronic 2017). In a survey of online forums, motivations for use low back pain, , and depression who was initially included opioid holidays, economic alternative to opioids prescribed oxycodone for chronic pain several years prior , and as opioid replacement therapy (Boyer et al., which was discontinued by providers after he developed 2007). Other reasons for use included self-treatment of anxi- medical misuse of opioids. He transitioned from oxycodone ety, depression and post-traumatic stress disorder (Grund- to kratom approximately 1-year before presenting to our clinic mann, 2017). The effects of kratom may be to treat his pain. He quickly developed a tolerance to kratom, due to its kappa-opioid antagonism (Lalanne et al., 2014; with escalating use and inability to stop using, and was Kruegel and Grundmann, 2017). Of note, depressive symp- spending approximately $2500 per month on kratom pur- toms also improved on buprenorphine, a mu-agonist/kappa- chased online. He reported withdrawal (anxiety, edginess, and antagonist. In a study of persons in substance use treatment, leg shaking) when without kratom and had used to kratom was primarily used to replace and prescription self-treat withdrawal. At time of presentation, he was using opioids, but rarely the drug of choice (Smith and Lawson, kratom to ‘‘feel normal’’ and for energy. Given his ongoing 2017). compulsive use, he sought treatment for his kratom addiction Given the increased use for self-treatment and lack of and was referred by his primary care doctor to the clinic’s regulation of kratom, there is need for more safety studies and buprenorphine practice. At time of buprenorphine initiation, evidence on addictive potential of kratom to educate the he had last used kratom 14 hours prior and oxycodone-acet- general public. At this time, there are no systematic human aminophen for a tooth extraction and reported mild with- studies on the addictive potential of kratom. However, in drawal symptoms (rhinorrhea and irritability). Baseline urine mouse studies, mitragynine showed similar addictive poten- toxicology was positive for /morphine and negative tial to morphine and with impairments in for all other substances. He successfully underwent home memory and learning (Yusoff et al., 2016). initiation of bup-nx 8-2 mg SL films with control of with- The legal status of kratom remains in flux. The Drug drawal symptoms and chronic pain. Over first month of Enforcement Agency attempted to make it Schedule I in 2016; follow-up, his buprenorphine dose was increased to 24 mg however, they withdrew this request after significant backlash daily (dosed 6 mg 4 times daily) to treat his pain. Seven (Prozialeck, 2016). It remains on the Drug Enforcement months later, he remains on bup-nx with follow-up urine Agency’s Drugs of Concern list and sale and possession toxicology positive for buprenorphine/norbuprenorphine has been banned in 6 states (Prozialeck, 2016). and negative for other opiates. Although some debate whether kratom is a true opioid or not, this case series shows that opioid agonist treatment DISCUSSION with buprenorphine-naloxone is effective for some patients Kratom is a growing and under-recognized drug of with kratom dependence and demonstrates 2 safe home misuse. Previous case reports document use of kratom for initiations of buprenorphine. This is first case series in the self-treatment of opioid withdrawal (Boyer et al., 2007; literature to report use of buprenorphine for treatment of

482 ß 2018 American Society of Addiction Medicine

Copyright © 2018 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited. J Addict Med  Volume 12, Number 6, November/December 2018 Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance

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Copyright © 2018 American Society of Addiction Medicine. Unauthorized reproduction of this article is prohibited.